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Biochem Biophys Res Commun. 2019 Mar 5. pii: S0006-291X(19)30282-7. doi: 10.1016/j.bbrc.2019.02.087. [Epub ahead of print]

PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.

Author information

1
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112 Blindern, 0317, Oslo, Norway.
2
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112 Blindern, 0317, Oslo, Norway; Oslo Center for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
3
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112 Blindern, 0317, Oslo, Norway; Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0424, Oslo, Norway. Electronic address: philc@medisin.uio.no.
4
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112 Blindern, 0317, Oslo, Norway. Electronic address: erwan.delbarre@medisin.uio.no.

Abstract

Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs. We show that loss of PML increases H3.3 deposition in subtelomeric, telomeric, pericentric and centromeric repeats in mouse embryonic fibroblasts, while other repeat classes are not affected. Expression of major satellite, minor satellite and telomeric non-coding transcripts is altered in Pml-null cells. In particular, telomeric Terra transcripts are strongly upregulated, in concordance with a marked reduction in H4K20me3 at these sites. Lastly, for most genes H3.3 enrichment or gene expression outcomes are independent of PML. Our data argue towards the importance of a PML-H3.3 axis in preserving a heterochromatin state at centromeres and telomeres.

KEYWORDS:

H3.3; Heterochromatin; Histone variant; PML; Telomere

PMID:
30850162
DOI:
10.1016/j.bbrc.2019.02.087

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